Researchers from the University of Chicago have been awarded a five-year, $1.5 million grant from the National Institutes of Health (NIH) to develop stimulated dendritic cell-derived exosomes that show remarkable promise as a treatment for multiple sclerosis and other neurological diseases involving loss of myelin, the insulation around nerve fibers.
Exosomes produced in the blood appear to play a causal role in the protective effects of regular exercise and learning, collectively known as "environmental enrichment," on the brain. These exosomes contain specific microRNAs that promote myelination of aging brain as well as brain damaged by multiple sclerosis modeled in animal brain tissues.
Based on this discovery, the Kraig lab is currently exploring the possibility of using cultured dendritic cells to recreate this effect. To do so will open new research opportunities for treatment of disorders that occur with a loss of myelin.
Led by Richard Kraig, MD, PhD, the William D. Mabie Professor in the Neurosciences in the department of Neurology at the University of Chicago, the research project is part of the Extracellular RNA Communication program, which aims to better understand extracellular RNA. This new initiative is supported by the NIH Common Fund, which funds high-impact, trans-NIH projects that have the potential to dramatically affect biomedical research over the next decade.
The Kraig project focuses on exosomes-small lipid vesicles that carry protein, RNA, and importantly, non-coding, extracellular microRNA, which are thought to enable cell-to-cell communication throughout the body.
Kraig and his team, which includes Aya Pusic and Kae Pusic, PhD, discovered that dendritic cells, professional antigen presenting cells of the immune system, can be stimulated by factors released during environmental enrichment to produce exosomes containing microRNAs that improve brain health.
When applied to cultured brain tissue or administered nasally to live animals, these dendritic cell-derived exosomes significantly increased baseline levels of myelin-the protective sheath around neurons, which is damaged in multiple sclerosis. Importantly, exosome administration also improved the recovery of demyelinated nerve cells, which serve as a model for multiple sclerosis.
"All evidence suggests these exosomes can be crafted into a novel therapy to treat multiple sclerosis," Kraig said. "The NIH Common Fund grant allows us to pursue the development of this promising discovery, while simultaneously characterizing its basic mechanisms."